PBAF regulates compartmentalization of actively transcribing chromatin hubs

Transcriptionally active genes contain acetyl-rich chromatin and are organized in distinct nuclear compartments that are spatially separated from transcriptionally inactive genes. It is not known how this compartmentalized acetylated chromatin is targeted and regulated by chromatin remodelers such as PBAF. Thus, we sought to understand how PBAF targets chromatin and modulates compartmentalization of transcriptionally active genes using live-cell single molecule fluorescence microscopy. Our work reveals chromatin hubs throughout the nucleus where PBAF cycles on and off the genome. Deletion of PBAF’s bromodomains impairs recognition of hubs and cycling on chromatin. Interestingly, markers for transcriptionally active and inactive genes can be found in compartments harboring acetylated chromatin at the periphery that is selectively recognized by PBAF via bromodomains. Defects in PBAF’s peripheral targeting lead to a select reduction in the size and number of compartments containing transcriptionally active genes. Our data, combined with previous work in Yeast and Drosophila, suggest that PBAF activity serves as a barrier to heterochromatin spreading. Overall, our findings suggest that chromatin compartments are highly structured with unique peripherally associated acetylation marks. PBAF utilizes these marks to help shape nuclear compartments containing transcriptionally active genes, thereby aiding genomic organization.